PROJECT SUMMARY In the United States, more than one out of every two women who conceive a child is overweight or obese. Obesity is a complex disorder and there are likely multiple causative factors emerging at various times through life. We have previously demonstrated in preclinical studies that offspring have altered metabolism when the fetuses are exposed to the consequences of maternal obesity in utero. The major effects relate to how the offspring metabolize energy and store excess energy. Offspring of obese women can spare and store more ingested energy as excess fat than offspring of lean women who burn more of their energy. Preliminary data from our ongoing clinical studies show that offspring of overweight women have increased fat mass at age 2 weeks and increased weight at age 2 years. One in two American infants will have been exposed to adverse metabolic conditions while developing in utero, and this increases the risk of developing obesity later in life. Although weight loss prior to pregnancy would be the preferred line of action, in light of the high incidence of unplanned pregnancies and the low success rate of significant weight loss among women, one critical strategy is to develop interventions during pregnancy to prevent childhood obesity. The objective of this proposal is to test an intervention that would reduce the effect of maternal obesity on the offspring and therefore prevent their risk of developing childhood obesity. The proposed study will test the efficacy of probiotics supplementation during pregnancy on preventing childhood obesity. To test these hypotheses we have designed a prospective randomized double blinded control trial. For this study we will recruit 104 obese women within the first 12 weeks of gestation and follow them throughout pregnancy and during their child's first two weeks of life. The obese women will be randomized to either a placebo (N=52) or to an intervention group (N=52). The intervention group will consist of a daily probiotic supplementation, whereas the control group will be administered a placebo. During the length of the study we will: carefully quantify maternal and child adiposity (fat mass); study maternal metabolism (dietary intake and energy expenditure); acquire dietary intakes and evaluate circulating levels of key metabolic markers. The specific aims will first demonstrate the potential for a probiotic intervention during gestation to improve maternal glucose use in obese women. For this aim, maternal fasting glucose and insulin levels will be assessed throughout pregnancy in the intervention group compared to the placebo group. The specific aims will also test whether a probiotic intervention during pregnancy in obese women alter offspring fat mass and decrease the risk of obesity in the offspring. To answer these questions, placenta, umbilical cord and cord blood will be obtained to study glucose, insulin and gene expression.